MRI with Magnetic Nanoparticles Monitors Downstream Anti-Angiogenic Effects of mTOR Inhibition
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To study the effect of mammalian target of rapamycin (mTOR) inhibition on angiogenesis with magnetic resonance imaging (MRI) using magnetic iron oxide nanoparticles (MNP).
One million CAK-1 renal cell carcinoma cells were subcutaneously implanted into each of 20 nude mice. When tumors reached ∼750 μl, four daily treatment arms began and continued for 4 weeks: rapamycin (mTOR inhibitor) 10 mg/kg/day; sorafenib (VEGF inhibitor) high dose (80 mg/kg/day) and low dose (30 mg/kg/day); and saline control. Weekly MRI (4.7 T Bruker Pharmascan) was performed before and after IV MION-48, a prototype MNP similar to MNP in clinical trials. Vascular volume fraction (VVF) was quantified as ΔR2 (from multi-contrast T2 sequences) and normalized to assumed muscle VVF of 3%. Linear regression compared VVF to microvascular density (MVD) as determined by histology.
VVF correlated with MVD (R2 = 0.95). VVF in all treatment arms differed from control (p < 0.05) and declined weekly with treatment. VVF changes with rapamycin were similar to high-dose sorafenib.
This study demonstrates noninvasive, in vivo anti-angiogenic monitoring using MRI of mTOR inhibition.
- MRI with Magnetic Nanoparticles Monitors Downstream Anti-Angiogenic Effects of mTOR Inhibition
Molecular Imaging and Biology
Volume 13, Issue 2 , pp 314-320
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- Magnetic resonance imaging
- Magnetic nanoparticle imaging
- Ultrasmall superparamagnetic iron oxide nanoparticle
- Renal cell cancer
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- Author Affiliations
- 1. Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
- 2. Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA
- 4. Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, 02114, USA
- 3. Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Boston, MA, USA